19-38605721-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001042600.3(MAP4K1):c.1210C>T(p.Arg404Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,605,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
MAP4K1
NM_001042600.3 missense
NM_001042600.3 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 2.38
Genes affected
MAP4K1 (HGNC:6863): (mitogen-activated protein kinase kinase kinase kinase 1) Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3169744).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP4K1 | NM_001042600.3 | c.1210C>T | p.Arg404Cys | missense_variant | 18/31 | ENST00000396857.7 | |
MAP4K1 | NM_007181.6 | c.1210C>T | p.Arg404Cys | missense_variant | 18/32 | ||
MAP4K1 | XM_011526404.2 | c.1330C>T | p.Arg444Cys | missense_variant | 19/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP4K1 | ENST00000396857.7 | c.1210C>T | p.Arg404Cys | missense_variant | 18/31 | 5 | NM_001042600.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152072Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000128 AC: 3AN: 234662Hom.: 0 AF XY: 0.0000154 AC XY: 2AN XY: 129680
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GnomAD4 exome AF: 0.0000117 AC: 17AN: 1453668Hom.: 0 Cov.: 34 AF XY: 0.0000111 AC XY: 8AN XY: 723548
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152072Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74272
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2021 | The c.1210C>T (p.R404C) alteration is located in exon 18 (coding exon 18) of the MAP4K1 gene. This alteration results from a C to T substitution at nucleotide position 1210, causing the arginine (R) at amino acid position 404 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
T;T;T
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at